WT1 gene (Wilms' tumor gene 1) has been identified as one of causative genes of Wilms' tumor that is a childhood renal tumor (Cell 60: 509, 1990, Nature 343: 774, 1990). WT1 gene encodes the transcription factor WT1 which plays an important role in many processes such as proliferation, differentiation and apoptosis of cells, and development of tissues (Int. Rev. Cytol. 181: 151, 1998). WT1 gene was originally defined as a tumor suppressor gene. However, subsequent studies revealed that WT1 gene is highly expressed in leukemia and various solid cancers including lung cancer and breast cancer, indicating that WT1 gene rather exerts an oncogenic function that promotes cancer growth. In addition, it was demonstrated that, when peripheral blood mononuclear cells positive for HLA-A*0201 or HLA-A*2402 were stimulated in vitro with WT1-derived peptides, peptide-specific cytotoxic T-lymphocytes (CTLs) were induced and killed leukemic or solid tumor cells which endogenously express WT1. These results demonstrated that WT1 is a promising target molecule of cancer immunotherapy (Int. J. Hematol 76: 127, 2002).
It has been reported that presence of helper T cells specific to cancer antigen is essential for effective induction of CTLs (Cancer. Res. 62: 6438, 2002).
Helper T cells (CD4-positive T cells) are induced (made proliferate) and activated when they recognize a complex of MHC class II molecule and antigen peptide on antigen-presenting cells. The activated helper T cells produce cytokines such as IL-2, IL-4, IL-5, IL-6, and/or interferons and mediate the growth, differentiation, and maturation of B cells. The activated helper T cells also function to promote the growth, differentiation or maturation of other subsets of T cells such as Tc and TD cells. Thus, the activated helper T cells can activate the immune system through the promotion of growth and activation of B and T cells. Therefore, it was suggested to be helpful to enhance functions of helper T cells being under the influence of MHC-class II-binding antigen peptide (also referred to as “helper peptide”), whereby efficacy (potency) of cancer vaccine in cancer immunotherapy (cancer vaccine therapy) is increased (J. Immunother., 24:195, 2001).
As for WT1-derived peptides, only one antigen peptide is known to bind to a subtype of MHC class II molecule, i.e., HLA-DRB1*0401 (Cancer Immunol. Immunother. 51:271, 2002). There are no WT1-derived peptides which have been reported to bind to different subtypes.